Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.978
Filtrar
1.
Nucleic Acids Res ; 48(3): 1583-1598, 2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-31956908

RESUMO

Cyclic dimeric 3'-5' guanosine monophosphate, c-di-GMP, is a ubiquitous second messenger controlling diverse cellular processes in bacteria. In streptomycetes, c-di-GMP plays a crucial role in a complex morphological differentiation by modulating an activity of the pleiotropic regulator BldD. Here we report that c-di-GMP plays a key role in regulating secondary metabolite production in streptomycetes by altering the expression levels of bldD. Deletion of cdgB encoding a diguanylate cyclase in Streptomycesghanaensis reduced c-di-GMP levels and the production of the peptidoglycan glycosyltransferase inhibitor moenomycin A. In contrast to the cdgB mutant, inactivation of rmdB, encoding a phosphodiesterase for the c-di-GMP hydrolysis, positively correlated with the c-di-GMP and moenomycin A accumulation. Deletion of bldD adversely affected the synthesis of secondary metabolites in S. ghanaensis, including the production of moenomycin A. The bldD-deficient phenotype is partly mediated by an increase in expression of the pleiotropic regulatory gene wblA. Genetic and biochemical analyses demonstrate that a complex of c-di-GMP and BldD effectively represses transcription of wblA, thus preventing sporogenesis and sustaining antibiotic synthesis. These results show that manipulation of the expression of genes controlling c-di-GMP pool has the potential to improve antibiotic production as well as activate the expression of silent gene clusters.


Assuntos
Proteínas de Bactérias/genética , Bambermicinas/biossíntese , Produtos Biológicos/metabolismo , GMP Cíclico/análogos & derivados , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/genética , Proteínas de Bactérias/antagonistas & inibidores , GMP Cíclico/genética , GMP Cíclico/metabolismo , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Escherichia coli/genética , Deleção de Genes , Regulação Bacteriana da Expressão Gênica/genética , Nucleotídeos/genética , Peptidoglicano Glicosiltransferase/antagonistas & inibidores , Fósforo-Oxigênio Liases/genética , Sistemas do Segundo Mensageiro/genética , Streptomycetaceae/genética , Streptomycetaceae/metabolismo , Fatores de Transcrição/antagonistas & inibidores
2.
Biosci Biotechnol Biochem ; 84(3): 433-444, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31738699

RESUMO

Ascomycota and basidiomycota fungi are prolific sources of biologically active natural products. Recent genomic data and bioinformatic analysis indicate that fungi possess a large number of biosynthetic gene clusters for bioactive natural products but more than 90% are silent. Heterologous expression in the filamentous fungi as hosts is one of the powerful tools to expression of the silent gene clusters. This review introduces recent studies on the total biosynthesis of representative family members via common platform intermediates, genome mining of novel di- and sesterterpenoids including detailed cyclization pathway, and development of expression host for basidiomycota genes with efficient genome editing method. In addition, this review will discuss the several strategies, for the generation of structural diversity, which are found through these studies.


Assuntos
Ascomicetos/metabolismo , Basidiomycota/metabolismo , Produtos Biológicos/metabolismo , Ascomicetos/genética , Basidiomycota/genética , Vias Biossintéticas/genética , Genes Fúngicos , Família Multigênica
3.
Recent Pat Biotechnol ; 14(1): 16-32, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31438835

RESUMO

BACKGROUND: Recently, it has been established that simultaneous saccharification and fermentation is a potent technique for the detoxification of harmful plant materials. OBJECTIVE: Following encouraging simultaneous medicinal applications of snail slime and yeast, we exploited their hydrolytic and fermentation potentials to prevent toxicities of the selected floras; Erythrodontium barteri (EB), bracken fern (BF), and crustose lichens (CL). The applicability of the saccharification process has been described in a patent (WO2005010193A2). METHODS: The plants were bioprocessed using snail digestive juice and yeast slurry and their health effects were evaluated. Seventy rats were divided equally into groups, treated with single doses of aqueous extracts of the plants and their bioprocessed forms, and compared with control rats. RESULTS: The plants showed very high antinutrients levels, which significantly reduced after SSF with enhanced flavonoids, alkaloids and phenols. Potential alterations of WBC differentials, RBC, liver and renal function markers indices were mitigated by bioprocessed extracts. MDA, SOD, GRase, XO and XDH levels in rats administered the bEB and CL were equivalent to the levels found for the control rats. Some bioprocessed plants produced unaltered insulin, ghrelin, and leptin levels. The bioprocessed extracts, when compared to the effects of unprocessed extracts, produced lower TNF-α, Caspase-3, and adiponectin levels and mitigated the potential suppression of Na+/K+-ATPase levels. Potential depletion of inhibin-B, testosterone, estrogen, and prolactin was mitigated after bioprocessing. CONCLUSION: This study, thus, validates the application of bioprocessing using snail digestive juice and yeast as an effective approach to reduce the potential toxicities of harmful plants.


Assuntos
Produtos Biológicos , Fígado , Extratos Vegetais , Animais , Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Biotransformação , Glicemia/efeitos dos fármacos , Embriófitas/química , Feminino , Testes Hematológicos , Líquens/química , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Patentes como Assunto , Extratos Vegetais/química , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacocinética , Extratos Vegetais/toxicidade , Ratos , Ratos Wistar , Caramujos/química , Leveduras/química
4.
Chemistry ; 26(6): 1196-1237, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31429510

RESUMO

All pharmaceutical products contain organic molecules; the source may be a natural product or a fully synthetic molecule, or a combination of both. Thus, it follows that organic chemistry underpins both existing and upcoming pharmaceutical products. The reverse relationship has also affected organic synthesis, changing its landscape towards increasingly complex targets. This Review article sets out to give a concise appraisal of this symbiotic relationship between organic chemistry and drug discovery, along with a discussion of the design concepts and highlighting key milestones along the journey. In particular, criteria for a high-quality compound library design enabling efficient virtual navigation of chemical space, as well as rise and fall of concepts for its synthetic exploration (such as combinatorial chemistry; diversity-, biology-, lead-, or fragment-oriented syntheses; and DNA-encoded libraries) are critically surveyed.


Assuntos
Descoberta de Drogas , Compostos Orgânicos/química , Bactérias/efeitos dos fármacos , Produtos Biológicos/química , Produtos Biológicos/metabolismo , DNA/química , Proteínas Facilitadoras de Transporte de Glucose/antagonistas & inibidores , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Ensaios de Triagem em Larga Escala , Compostos Orgânicos/síntese química , Compostos Orgânicos/farmacologia , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia
5.
Phytochemistry ; 170: 112214, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31794881

RESUMO

In recent years, ionic liquids and deep eutectic solvents (DESs) have gained increasing attention due to their ability to extract and solubilize metabolites and biopolymers in quantities far beyond their solubility in oil and water. The hypothesis that naturally occurring metabolites are able to form a natural deep eutectic solvent (NADES), thereby constituting a third intracellular phase in addition to the aqueous and lipid phases, has prompted researchers to study the role of NADES in living systems. As an excellent solvent for specialized metabolites, formation of NADES in response to dehydration of plant cells could provide an appropriate environment for the functional storage of enzymes during drought. Using the enzymes catalyzing the biosynthesis of the defense compound dhurrin as an experimental model system, we demonstrate that enzymes involved in this pathway exhibit increased stability in NADES compared with aqueous buffer solutions, and that enzyme activity is restored upon rehydration. Inspired by nature, application of NADES provides a biotechnological approach for long-term storage of entire biosynthetic pathways including membrane-anchored enzymes.


Assuntos
Produtos Biológicos/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Nitrilos/metabolismo , Compostos Fitoquímicos/biossíntese , Sorghum/química , Produtos Biológicos/química , Estrutura Molecular , Nitrilos/química , Compostos Fitoquímicos/química , Solubilidade , Solventes , Sorghum/citologia , Sorghum/metabolismo
6.
J Ethnopharmacol ; 247: 112201, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31499140

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Bergenin is a well-known active compound that exhibits antioxidant, antiarrhythmic, hepatoprotective, and anti-inflammatory activities. However, the resource reserve of Rodgersia sambucifolia, one of the main raw materials for extracting bergenin, have sharply declined, and the bergenin content in different germplasms differs vastly, resulting in a serious shortage of the market supply of bergenin. AIM OF THE STUDY: To investigate the influence of genetic diversity and environmental factors on bergenin content in Rodgersia sambucifolia. MATERIALS AND METHODS: Fifty Rodgersia sambucifolia samples with a growth period of 2-3 years were collected from different areas across China and the bergenin content was determined via HPLC. Meanwhile the total genomic DNA was extracted and ISSR was performed. The bergenin content as measured using HPLC and the environmental data gathered from the meteorological stations and field work were combined and analyzed using correlation tests in XLSTAT 2018 to detect the key factors affecting bergenin content. The genetic UPGMA tree constructed based on genetic distances of the 50 samples and the chemical dendrogram constructed according to the distance between the bergenin content were compared to determine the correlation between genetic and chemical differentiation. RESULTS: Among the 50 individuals, bergenin content varied from 2.83 to 12.54%, with the highest content being 4.43-fold that of the lowest content. The survey of the 50 individuals produced a total of 193 amplified bands, 187 of which were polymorphic (96.89%). In the study, bergenin content was positively correlated with annual mean temperature (AMT) (r = 0.583, P < 0.0001) and 1-12 month monthly mean temperature (MMT) (P < 0.0001). A comparison of the genetic dendrogram with the AHC dendrogram found no corresponding relationship between them. Mantel correlation analyses also showed that there was no significant correlation between them (r = 0.144). CONCLUSIONS: There were large differences in bergenin content among different germplasms that were not correlated with the high genetic variation in Rodgersia sambucifolia but were significantly correlated with environmental factors, such as temperature. This study lays the foundation for subsequent superior germplasm selection and artificial breeding of Rodgersia sambucifolia to improve the bergenin content and meet market demands.


Assuntos
Benzopiranos/metabolismo , Produtos Biológicos/metabolismo , Vias Biossintéticas/genética , Variação Genética , Saxifragaceae/metabolismo , Antineoplásicos/isolamento & purificação , Antineoplásicos/metabolismo , Antioxidantes/isolamento & purificação , Antioxidantes/metabolismo , Benzopiranos/isolamento & purificação , Produtos Biológicos/isolamento & purificação , China , DNA de Plantas/genética , DNA de Plantas/isolamento & purificação , Filogenia , Melhoramento Vegetal , Saxifragaceae/genética , Sementes/genética , Sementes/metabolismo , Temperatura Ambiente
7.
BMC Complement Altern Med ; 19(1): 350, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31806003

RESUMO

BACKGROUND: The use of deer velvet antler (DVA) as a potent traditional medicine ingredient goes back for over 2000 years in Asia. Increasingly, though, DVA is being included as a high protein functional food ingredient in convenient, ready to consume products in Korea and China. As such, it is a potential source of endogenous bioactive peptides and of 'cryptides', i.e. bioactive peptides enzymatically released by endogenous proteases, by processing and/or by gastrointestinal digestion. Fermentation is an example of a processing step known to release bioactive peptides from food proteins. In this study, we aimed to identify in silico bioactive peptides and cryptides in DVA, before and after fermentation, and subsequently to validate the major predicted bioactivity by in vitro analysis. METHODS: Peptides that were either free or located within proteins were identified in the DVA samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by database searching. Bioactive peptides and cryptides were identified in silico by sequence matching against a database of known bioactive peptides. Angiotensin-converting enzyme (ACE) inhibitory activity was measured by a colorimetric method. RESULTS: Three free bioactive peptides (LVVYPW, LVVYPWTQ and VVYPWTQ) were solely found in fermented DVA, the latter two of which are known ACE inhibitors. However matches to multiple ACE inhibitor cryptides were obtained within protein and peptide sequences of both unfermented and fermented DVA. In vitro analysis showed that the ACE inhibitory activity of DVA was more pronounced in the fermented sample, but both unfermented and fermented DVA had similar activity following release of cryptides by simulated gastrointestinal digestion. CONCLUSIONS: DVA contains multiple ACE inhibitory peptide sequences that may be released by fermentation or following oral consumption, and which may provide a health benefit through positive effects on the cardiovascular system. The study illustrates the power of in silico combined with in vitro methods for analysis of the effects of processing on bioactive peptides in complex functional ingredients like DVA.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Chifres de Veado/química , Produtos Biológicos , Peptídeos , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Animais , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Simulação por Computador , Cervos , Digestão , Fermentação , Modelos Biológicos , Peptídeos/química , Peptídeos/metabolismo
8.
World J Microbiol Biotechnol ; 35(11): 177, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31696403

RESUMO

Plant biostimulants are defined as materials containing microorganisms or substances whose function when applied to plants or the rhizosphere is to stimulate natural mechanisms to enhance plant growth, nutrient use efficiency, tolerance to abiotic stressors and crop quality, independent of their nutrient content. In agriculture, seaweeds (Macroalgae) have been used in the production of plant biostimulants while microalgae still remain unexploited. Microalgae are single cell microscopic organisms (prokaryotic or eukaryotic) that grow in a range of aquatic habitats, including, wastewaters, pounds, lakes, rivers, oceans, and even humid soils. These photosynthetic microorganisms are widely described as renewable sources of biofuels, bioingredients and biologically active compounds, such as polyunsaturated fatty acids (PUFAs), carotenoids, phycobiliproteins, sterols, vitamins and polysaccharides, which attract considerable interest in both scientific and industrial communities. Microalgae polysaccharides have so far proved to have several important biological activities, making them biomaterials and bioactive products of increasing importance for a wide range of applications. The present review describes microalgae polysaccharides, their biological activities and their possible application in agriculture as a potential sustainable alternative for enhanced crop performance, nutrient uptake and resilience to environmental stress. This review does not only present a comprehensive and systematic study of Microalgae polysaccharides as plant biostimulants but considers the fundamental and innovative principles underlying this technology.


Assuntos
Produtos Agrícolas/efeitos dos fármacos , Microalgas/metabolismo , Desenvolvimento Vegetal/efeitos dos fármacos , Polissacarídeos/metabolismo , Produtos Biológicos/metabolismo , Biotecnologia/métodos , Produtos Agrícolas/metabolismo , Estresse Fisiológico/efeitos dos fármacos
9.
Sheng Wu Gong Cheng Xue Bao ; 35(10): 1889-1900, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31668036

RESUMO

Novel natural products have always been the most important sources for discovery of new drugs. Since the end of the 20th century, advances in genomics technology have contributed to decode and analyze numerous genomes, revealing remarkable potential for production of new natural products in organisms. However, this potential is hampered by laboratory culture conditions. Therefore, the integration of all these new advances is necessary to unveil these treasures, addressing the rise in resistance to antibiotics. In this review, we discuss the strategies of genome mining, inducing the expression of silent biosynthetic gene clusters and construction of biological chassis.


Assuntos
Produtos Biológicos/metabolismo , Vias Biossintéticas/genética , Genômica , Animais , Genoma/genética , Família Multigênica/genética
10.
Curr Top Med Chem ; 19(31): 2868-2918, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31724505

RESUMO

Actinomycetes is an abundant resource for discovering a large number of lead compounds, which play an important role in microbial drug discovery. Compared to terrestrial microorganisms, marine actinomycetes have unique metabolic pathways because of their special living environment, which has the potential to produce a variety of bioactive substances. In this paper, secondary metabolites isolated from marine actinomycetes are reviewed (2013-2018), most of which exhibited cytotoxic, antibacterial, and antiviral biological activities.


Assuntos
Actinobacteria/química , Antibacterianos/metabolismo , Antineoplásicos/metabolismo , Antivirais/metabolismo , Produtos Biológicos/metabolismo , Actinobacteria/metabolismo , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antivirais/química , Antivirais/isolamento & purificação , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Humanos
11.
Curr Top Med Chem ; 19(28): 2567-2578, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31654510

RESUMO

BACKGROUND: Biofilm is a critical virulence factor associated with the strains of Candida spp. pathogens as it confers significant resistance to the pathogen against antifungal drugs. METHODS: A systematic review of the literature was undertaken by focusing on natural products, which have been reported to inhibit biofilms produced by Candida spp. The databases explored were from PubMed and Google Scholar. The abstracts and full text of the manuscripts from the literature were analyzed and included if found significant. RESULTS: Medicinal plants from the order Lamiales, Apiales, Asterales, Myrtales, Sapindales, Acorales, Poales and Laurales were reported to inhibit the biofilms formed by Candida spp. From the microbiological sources, lactobacilli, Streptomyces chrestomyceticus and Streptococcus thermophilus B had shown the strong biofilm inhibition potential. Further, the diverse nature of the compounds from classes like terpenoids, phenylpropanoid, alkaloids, flavonoids, polyphenol, naphthoquinone and saponin was found to be significant in inhibiting the biofilm of Candida spp. CONCLUSION: Natural products from both plant and microbial origins have proven themselves as a goldmine for isolating the potential biofilm inhibitors with a specific or multi-locus mechanism of action. Structural and functional characterization of the bioactive molecules from active extracts should be the next line of approach along with the thorough exploration of the mechanism of action for the already identified bioactive molecules.


Assuntos
Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Produtos Biológicos/farmacologia , Candida/efeitos dos fármacos , Candida/patogenicidade , Antifúngicos/química , Antifúngicos/metabolismo , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Candida/classificação , Humanos , Testes de Sensibilidade Microbiana , Plantas Medicinais , Especificidade da Espécie
12.
Chem Asian J ; 14(22): 4001-4012, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31609526

RESUMO

This Minireview describes the exploitation of certain enzymatically derived, readily accessible, and enantiomerically pure cis-1,2-dihydrocatechols as starting materials in the chemical synthesis of a range of biologically active natural products, most notably sesquiterpenoids and alkaloids.


Assuntos
Produtos Biológicos/metabolismo , Dioxigenases/metabolismo , Produtos Biológicos/química , Catecóis/química , Catecóis/metabolismo , Ciclitóis/química , Ciclitóis/metabolismo , Reação de Cicloadição , Oxigenases/metabolismo , Estereoisomerismo
13.
Microbiology ; 165(11): 1169-1180, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31592756

RESUMO

Polar and subpolar ecosystems are highly vulnerable to global climate change with consequences for biodiversity and community composition. Bacteria are directly impacted by future environmental change and it is therefore essential to have a better understanding of microbial communities in fluctuating ecosystems. Exploration of Polar environments, specifically sediments, represents an exciting opportunity to uncover bacterial and chemical diversity and link this to ecosystem and evolutionary parameters. In terms of specialized metabolite production, the bacterial order Actinomycetales, within the phylum Actinobacteria are unsurpassed, producing 10 000 specialized metabolites accounting for over 45 % of all bioactive microbial metabolites. A selective isolation approach focused on spore-forming Actinobacteria of 12 sediment cores from the Antarctic and sub-Arctic generated a culture collection of 50 strains. This consisted of 39 strains belonging to rare A ctinomycetales genera including Microbacterium, Rhodococcus and Pseudonocardia. This study used a combination of nanopore sequencing and molecular networking to explore the community composition, culturable bacterial diversity, evolutionary relatedness and specialized metabolite potential of these strains. Metagenomic analyses using MinION sequencing was able to detect the phylum Actinobacteria across polar sediment cores at an average of 13 % of the total bacterial reads. The resulting molecular network consisted of 1652 parent ions and the lack of known metabolite identification supports the argument that Polar bacteria are likely to produce previously unreported chemistry.


Assuntos
Actinobacteria/genética , Actinobacteria/metabolismo , Actinobacteria/classificação , Actinobacteria/isolamento & purificação , Regiões Antárticas , Regiões Árticas , Biodiversidade , Produtos Biológicos/classificação , Produtos Biológicos/metabolismo , DNA Bacteriano/genética , Evolução Molecular , Sedimentos Geológicos/microbiologia , Metagenômica , Microbiota/genética , Filogenia , RNA Ribossômico 16S/química
14.
Curr Top Med Chem ; 19(25): 2348-2356, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31648637

RESUMO

Acetoin is an important four-carbon compound that has many applications in foods, chemical synthesis, cosmetics, cigarettes, soaps, and detergents. Its stereoisomer (S)-acetoin, a high-value chiral compound, can also be used to synthesize optically active drugs, which could enhance targeting properties and reduce side effects. Recently, considerable progress has been made in the development of biotechnological routes for (S)-acetoin production. In this review, various strategies for biological (S)- acetoin production are summarized, and their constraints and possible solutions are described. Furthermore, future prospects of biological production of (S)-acetoin are discussed.


Assuntos
Acetoína/metabolismo , Produtos Biológicos/metabolismo , Acetoína/química , Produtos Biológicos/química , Conformação Molecular
15.
Artigo em Inglês | MEDLINE | ID: mdl-31564305

RESUMO

Non-heme iron enzymes catalyze a wide range of chemical transformations, serving as one of the key types of tailoring enzymes in the biosynthesis of natural products. Hydroxylation reaction is the most common type of reactions catalyzed by these enzymes and hydroxylation reactions have been extensively investigated mechanistically. However, the mechanistic details for other types of transformations remain largely unknown or unexplored. In this paper, we present some of the most recently discovered transformations, including endoperoxidation, orthoester formation, cyclopropanation, oxidative C-C and C-S bond formation reactions. In addition, many of them are multi-functional enzymes, which further complicate their mechanistic investigations. In this work, we summarize their biosynthetic pathways, with special emphasis on the mechanistic details available for these newly discovered enzymes.


Assuntos
Produtos Biológicos/metabolismo , Fungos/enzimologia , Ferroproteínas não Heme/metabolismo , Produtos Biológicos/química , Proteínas Fúngicas , Modelos Moleculares , Ferroproteínas não Heme/química , Conformação Proteica
16.
Comput Biol Chem ; 83: 107112, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31480006

RESUMO

Prostate cancer is a common cause of death in men and a novel treating methods should be developed. In order to find a new drug for prostate cancer, a series of novel conformationally constrained analogues of (+)-goniofufurone and 7-epi-(+)-goniofufurone, as well as the newly synthesized styryl lactones containing the cinnamic acid ester groups were evaluated for in vitro cytotoxicity against prostate cancer cell (PC-3). Furthermore, prediction of physicochemical characteristics and drugability as well as in silico ADME-Tox tests of investigated compounds were performed. The 3D-QSAR model was established using the comparative molecular field analysis method. According to obtained results, the tricyclic compounds 9 and 10 had the highest potency with IC50 < 20 µM. Evaluation of structural features through 3D-QSAR model identified steric field feature on the cinnamic acid ester groups at C-7 as a crucial for the cytotoxic activity. This research suggests that most of the analysed compounds have desirable properties for drug candidates and high potential in drug development, which recommend them for further research in treatment of prostate cancer. Furthermore, obtained 3D-QSAR model is able to successfully identify styryl lactones that have significant cytotoxic activity and provide information for screening and design of novel inhibitors against PC-3 cell line that could be used as drugs in treatment of the prostate cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Produtos Biológicos/farmacologia , Lactonas/farmacologia , Relação Quantitativa Estrutura-Atividade , Estirenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/metabolismo , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Proliferação de Células/efeitos dos fármacos , Simulação por Computador , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lactonas/química , Lactonas/metabolismo , Modelos Moleculares , Células PC-3 , Estirenos/química , Estirenos/metabolismo
17.
Org Biomol Chem ; 17(40): 8943-8957, 2019 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-31482157

RESUMO

Diterpene pyrones (DTPs) are a group of well-known, mainly fungal, natural products, first isolated in 1966. As the name indicates, they are composed of two main structural features: a diterpenyl moiety and a pyrone ring. Various names have been given to this class of metabolites; however, biogenetic evidence indicates that they originate through the same metabolic pathway. Based on their biosynthesis, which leads to differences in their structural architecture, the DTPs can be classified into three main types. In addition to their intriguing chemistry, these compounds demonstrate a wide range of biological activities rendering them a desirable target for total synthesis. To date, sixty-seven DTPs have been isolated from various fungal species, with one example originating from the plant kingdom. This review aims at unifying the classification of these compounds, in addition to presenting a detailed description of their isolation, bioactivities, biosynthesis, and total synthesis.


Assuntos
Produtos Biológicos/química , Produtos Biológicos/metabolismo , Diterpenos/química , Diterpenos/metabolismo , Pironas/química , Pironas/metabolismo , Produtos Biológicos/síntese química , Diterpenos/síntese química , Estrutura Molecular , Pironas/síntese química
19.
Mar Drugs ; 17(8)2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398953

RESUMO

Marine organisms produce a large array of natural products with relevance in drug discovery. These compounds have biological activities such as antioxidant, antibacterial, antitumor, antivirus, anticoagulant, anti-inflammatory, antihypertensive, antidiabetic, and so forth. Consequently, several of the metabolites have made it to the advanced stages of clinical trials, and a few of them are commercially available. In this review, novel information on natural products isolated from marine microorganisms, microalgae, and macroalgae are presented. Given due research impetus, these marine metabolites might emerge as a new wave of promising drugs.


Assuntos
Organismos Aquáticos/metabolismo , Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Microalgas/metabolismo , Alga Marinha/metabolismo , Animais , Descoberta de Drogas/métodos , Humanos
20.
Phytochemistry ; 167: 112084, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31415913

RESUMO

The medicinal plant drug "Tiliae flos" consists of the botanical flowers and bracts of Tilia sp., gathered almost exclusively during flowering. In this study, we examined the changes in the metabolome of specialized products in the bracts of Tilia platyphyllos from the appearance of the organ till the onset of senescence by LC-ESI-MS and data mining. A set of 504 natural products were detected, 241 of which showed significant seasonal variation (p < 9.92E-5). Seven compounds were quantified and an additional 45 were putatively identified. These included flavonoid glycosides, catechins, procyanidins, quinic acid derivatives (including chlorogenic acid) and coumarins. Compared to bracts during flowering, young tissues were characterized by a relatively high diversity of polyphenolic substances. Higher amounts of flavonol glycosides (quercetin, kaempferol), catechins and derivatives have been observed. Deoxyhexosides were almost exclusive to this phenological stage. Changes of about one order of magnitude were not uncommon. For some substances, 5-fold differences were observed (calibration with authentic standards). Some compounds (e.g. the coumarin fraxin) were more prominent at the late fruit growth stage. It was shown that bracts gathered before or after flowering could potentially be therapeutically useful. Changes are rapid during the early phase of bract development: three different groups of compounds presented their maxima during the first 32 days. Considering seasonal variation is of extreme importance during bioactivity tests and screening candidate sources for bioactive natural products. In the case of T. platyphyllos, young and old bracts can be of interest because of their high diversity of distinct specialized metabolites.


Assuntos
Metabolômica , Tilia/crescimento & desenvolvimento , Tilia/metabolismo , Produtos Biológicos/metabolismo , Estações do Ano
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA